Regional nodal failure after conservative surgery and radiotherapy for early-stage breast carcinoma.

We retrospectively analyzed the likelihood of regional nodal failure (RNF) for 1,624 patients with stage I or II invasive breast carcinoma treated with conservative surgery and radiotherapy (RT) at the Joint Center for Radiation Therapy (JCRT) between 1968 and 1985. The median follow-up time was 77 months. RNF was the first site of failure for 38 of the 1,624 patients (2.3%). The incidence of axillary failure for patients undergoing axillary dissection (AXD) who were irradiated to the breast only was 2.1% (nine of 420) for patients with negative nodes and 2.1% (one of 47) for patients with one to three positive nodes. The incidence of supraclavicular failure in these two groups was 1.9% (eight of 420) and 0% (zero of 47), respectively. The incidences of axillary and supraclavicular failure in patients without clinically suspicious axillary involvement who did not have AXD but were treated with RT were 0.8% (three of 355) and 0.3% (one of 364), respectively. Despite various combinations of salvage surgery, RT, and systemic therapy, only 47% of patients (18 of 38) achieved complete regional control after nodal relapse. We conclude that RNF is uncommon in patients treated to the breast alone following an adequate AXD when the axillary nodes are negative or when one to three nodes are positive. RNF is also uncommon in patients with a clinically uninvolved axilla treated with nodal RT without AXD. Symptoms of RNF can be controlled in most but not all patients. Further study is needed to determine if the benefits of RT in preventing a small number of symptomatic RNF outweigh the potential toxicity for any subgroup of patients.

Long-term radiation complications following conservative surgery (CS) and radiation therapy (RT) in patients with early stage breast cancer.

The frequency of brachial plexopathy, rib fracture, tissue necrosis, pericarditis, and second non-breast malignancies occurring in the treatment field among 1624 patients with early stage breast cancer treated with conservative surgery and radiation therapy at the Joint Center for Radiation Therapy between 1968 and 1985 is reported. The median follow-up time for survivors was 79 months (range 5-233 months). Brachial plexopathy was related to the use of a third field, the use of chemotherapy and the total dose to the axilla. Brachial plexopathy developed in 20 of 1117 women (1.8%) who received supraclavicular irradiation with or without axillary irradiation. The median time to its occurrence was 10.5 months (range 1.5-77 mo), and the majority (80%) of cases completely resolved. Among patients treated with a three-field technique, the incidence of brachial plexopathy was 1.3% (13/991) in patients treated with a dose to the axilla of less than or equal to 50 Gy, compared with 5.6% (7/126) in women treated with an axillary dose of greater than 50 Gy. The incidence of brachial plexopathy was 4.5% (15/330) among patients receiving chemotherapy, compared with 0.6% (5/787) when chemotherapy was not used (p less than 0.0001). Rib fracture was seen in 29 patients (1.8%), at a median time of 12 months following treatment (range 1-57). In all cases, the rib fracture healed without intervention. The incidence of rib fracture was 2.2% (28/1300) among patients treated on a 4 MV linear accelerator, compared with 0.4% (1/276) for patients treated on a 6 or 8 MV machine (p = 0.05). Of patients treated on a 4 MV machine, 0.4% (1/279) developed a rib fracture when a whole breast dose of 45 Gy or less was given, 1.4% (10/725) after receiving between 45 and 50 Gy, and 5.7% (17/296) following 50 Gy or higher. Tissue necrosis requiring surgical correction developed in three patients (0.18%) 22, 25, and 114 months after treatment. Presumed pericarditis (requiring hospitalization) was seen in 0.4% of women (3/831) who received radiation therapy to the left breast 2, 2, and 11 months after the start of treatment. Three women (0.18%) developed sarcomas in the treatments field at 72, 107, and 110 months, for a 10-year actuarial rate of 0.8%. Two of these sarcomas developed in areas of probable match-line overlap. One patient (0.06%) developed an in-field basal cell carcinoma at 42 months. In conclusion, the risk of significant complications following conservative surgery and radiation therapy for early stage breast cancer is low.(ABSTRACT TRUNCATED AT 400 WORDS)

Elevation of mouse kidney thiol content following administration of glutathione.

We have found that kidney glutathione and cysteine content in C3H mice can be increased by intraperitoneal administration of either glutathione (GSH) or glutathione disulfide (GSSG). Kidney thiol content is maximal 20-60 min after administration of 1000 mg/kg glutathione and returns to normal values by 2 h. The same time-course of thiol perturbation was observed when acivicin, an inhibitor of gamma-glutamyl transpeptidase, was administered 15 min prior to GSSG administration. The increase in kidney thiols after GSSG administration appears to saturate, with little additional increase as the administered dose is increased above 750 mg/kg. There was no significant change in liver GSH or cysteine after GSSG administration. We suggest that glutathione administration may provide a strategy for selective radioprotection or chemoprotection of specialized cells which can effectively utilize systemic GSH precursors.

Radioprotection of DNA in isolated nuclei by naturally occurring thiols at intermediate oxygen tension.

Incubation of isolated Chinese hamster ovary cell nuclei, equilibrated in an atmosphere containing 2% O2, with glutathione, cysteine, or cysteamine resulted in a decrease in the number of X-ray-induced DNA double-strand breaks (DSBs), determined by pH 9.0 filter elution. In the absence of exogenous thiol, no sensitization was observed with the addition of N-ethylmaleimide, indicating that endogenous thiols were not present at significant levels. Protection by 0.3 mM glutathione was not enhanced by the addition of exogenous glutathione S-transferases or by glutathione peroxidase. The data were analyzed according to a simple competition model with various hypotheses. Cysteamine was more than an order of magnitude more effective than the other thiols tested, on a molar basis, in preventing DSB formation. Depending on the hypothesis used to evaluate the data, glutathione was either much less effective, on a molar basis, in preventing the bulk of the DSBs or was capable of preventing only approximately 55% of the damage, regardless of concentration. These data suggest that natural thiols other than glutathione may contribute to cellular radioprotection even if their concentration is much lower than that of glutathione. The data also suggest that despite the relative inefficiency of glutathione as a radioprotector, some areas of oxygenated tissues--where the oxygen tension falls below 2%--may be protected by glutathione concentrations in the physiological range of 3-20 mM.

Smoke-induced germination of succulents (Mesembryanthemaceae) from fire-prone and fire-free habitats in South Africa.

Previous studies have shown germination to be stimulated by fire-related cues such as heat and charate extract and, more recently, plant-derived smoke extract. However, smoke extract has not been tested on non-fire-prone species. We hypothesized that smoke-induced germination would be restricted to fire-prone species and investigated responses of members of the family Mesembryanthemaceae which has genera confined to fire-prone and to non-fire-prone habitats as well as genera with species across both habitats. Results of germination trials of smoke effects did not support the hypothesis. Plant-derived smoke extract stimulated germination in both fire-prone and non-fire-prone species. These results cast some doubt on the ecological significance of smoke as a fire-related cue and we suggest that investigation of effects of fire-related cues on non-fire prone species may throw light on general mechanisms of germination.

Radiation therapy to the breast: practical aspects.

The use of conservative surgery and radiation therapy in the treatment of early stage breast cancer is increasing. Several prospective randomized trials have reported survival rates for patients treated with conservative surgery and radiation therapy equivalent to those of patients treated with mastectomy. This paper will review the evidence supporting the use of conservative surgery and radiation therapy, discuss the process of patient selection, review the technique and complications of radiation treatment, and outline follow-up for women after conservative surgery and radiation therapy.

Definitive radiation therapy in the management of symptomatic patients with optic glioma. Survival and long-term effects.

We reviewed 24 children who had symptomatic gliomas that involved the optic chiasm and were treated with definitive radiation therapy from 1971 to 1986. In eight patients (33%), histologic confirmation of low-grade astrocytoma was obtained. Patients had radiation therapy only if there was evidence of visual deterioration or other clinical or radiographic evidence of disease progression. Radiation doses ranged from 4500 to 5660 cGy (median, 5400 cGy) with up to a 17-year follow-up period (median, 6 years). The 6-year actuarial freedom from disease progression and overall 6-year survival are 88% and 100%, respectively. Visual improvement or stabilization was seen in 21 (91%) patients after radiation. A high incidence of endocrine abnormalities is reported, with 15 of the 18 patients evaluated after treatment showing growth hormone deficiency. We conclude that definitive radiation therapy is associated with tumor control in most of the patients with progressive optic chiasm gliomas. However, neuropsychiatric and endocrine abnormalities are significant problems that need additional evaluation in these children.